Using Expectancy Theory to quantitatively dissociate the neural representation of motivation from its influential factors in the human brain: An fMRI study.

Researchers have yet to apply a formal operationalized theory of motivation to neurobiology that would more accurately and precisely define neural activity underlying motivation. We overcome this challenge with the novel application of the Expectancy Theory of Motivation to human fMRI to identify brain activity that explicitly reflects motivation. Expectancy Theory quantitatively describes how individual constructs determine motivation by defining motivation force as the product of three variables: expectancy - belief that effort will better performance; instrumentality - belief that successful performance leads to particular outcome, and valence - outcome desirability. Here, we manipulated information conveyed by reward-predicting cues such that relative cue-evoked activity patterns could be statistically mapped to individual Expectancy Theory variables. The variable associated with activity in any voxel is only reported if it replicated between two groups of healthy participants. We found signals in midbrain, ventral striatum, sensorimotor cortex, and visual cortex that specifically map to motivation itself, rather than other factors. This is important because, for the first time, it empirically clarifies approach motivation neural signals during reward anticipation. It also highlights the effectiveness of the application of Expectancy Theory to neurobiology to more precisely and accurately probe motivation neural correlates than has been achievable previously.

Neurobiological correlates of impulsivity in healthy adults: Lower prefrontal gray matter volume and spontaneous eye-blink rate but greater resting-state functional connectivity in basal ganglia-thalamo-cortical circuitry.

Studies consistently implicate aberrance of the brain's reward-processing and decision-making networks in disorders featuring high levels of impulsivity, such as attention-deficit hyperactivity disorder, substance use disorder, and psychopathy. However, less is known about the neurobiological determinants of individual differences in impulsivity in the general population. In this study of 105 healthy adults, we examined relationships between impulsivity and three neurobiological metrics - gray matter volume, resting-state functional connectivity, and spontaneous eye-blink rate, a physiological indicator of central dopaminergic activity. Impulsivity was measured both by performance on a task of behavioral inhibition (go/no-go task) and by self-ratings of attentional, motor, and non-planning impulsivity using the Barratt Impulsiveness Scale (BIS-11). Overall, we found that less gray matter in medial orbitofrontal cortex and paracingulate gyrus, greater resting-state functional connectivity between nodes of the basal ganglia-thalamo-cortical network, and lower spontaneous eye-blink rate were associated with greater impulsivity. Specifically, less prefrontal gray matter was associated with higher BIS-11 motor and non-planning impulsivity scores, but was not related to task performance; greater correlated resting-state functional connectivity between the basal ganglia and thalamus, motor cortices, and prefrontal cortex was associated with worse no-go trial accuracy on the task and with higher BIS-11 motor impulsivity scores; lower spontaneous eye-blink rate was associated with worse no-go trial accuracy and with higher BIS-11 motor impulsivity scores. These data provide evidence that individual differences in impulsivity in the general population are related to variability in multiple neurobiological metrics in the brain's reward-processing and decision-making networks.

Fornix Microstructure and Memory Performance Is Associated with Altered Neural Connectivity during Episodic Recognition.

OBJECTIVES: The purpose of this study was to assess whether age-related differences in white matter microstructure are associated with altered task-related connectivity during episodic recognition. METHODS: Using functional magnetic resonance imaging and diffusion tensor imaging from 282 cognitively healthy middle-to-late aged adults enrolled in the Wisconsin Registry for Alzheimer's Prevention, we investigated whether fractional anisotropy (FA) within white matter regions known to decline with age was associated with task-related connectivity within the recognition network. RESULTS: There was a positive relationship between fornix FA and memory performance, both of which negatively correlated with age. Psychophysiological interaction analyses revealed that higher fornix FA was associated with increased task-related connectivity amongst the hippocampus, caudate, precuneus, middle occipital gyrus, and middle frontal gyrus. In addition, better task performance was associated with increased task-related connectivity between the posterior cingulate gyrus, middle frontal gyrus, cuneus, and hippocampus. CONCLUSIONS: The findings indicate that age has a negative effect on white matter microstructure, which in turn has a negative impact on memory performance. However, fornix microstructure did not significantly mediate the effect of age on performance. Of interest, dynamic functional connectivity was associated with better memory performance. The results of the psychophysiological interaction analysis further revealed that alterations in fornix microstructure explain-at least in part-connectivity among cortical regions in the recognition memory network. Our results may further elucidate the relationship between structural connectivity, neural function, and cognition.

Midlife measurements of white matter microstructure predict subsequent regional white matter atrophy in healthy adults.

OBJECTIVES: Although age-related brain changes are becoming better understood, midlife patterns of change are still in need of characterization, and longitudinal studies are lacking. The aim of this study was to determine if baseline fractional anisotropy (FA), obtained from diffusion tensor imaging (DTI) predicts volume change over a 4-year interval. EXPERIMENTAL DESIGN: Forty-four cognitively healthy middle-age adults underwent baseline DTI and longitudinal T1-weighted magnetic resonance imaging. Tensor-based morphometry methods were used to evaluate volume change over time. FA values were extracted from regions of interest that included the cingulum, entorhinal white matter, and the genu and splenium of the corpus callosum. Baseline FA was used as a predictor variable, whereas gray and white matter atrophy rates as indexed by Tensor-based morphometry were the dependent variables. PRINCIPAL OBSERVATIONS: Over a 4-year period, participants showed significant contraction of white matter, especially in frontal, temporal, and cerebellar regions (P < 0.05, corrected for multiple comparisons). Baseline FA in entorhinal white matter, genu, and splenium was associated with longitudinal rates of atrophy in regions that included the superior longitudinal fasciculus, anterior corona radiata, temporal stem, and white matter of the inferior temporal gyrus (P < 0.001, uncorrected for multiple comparisons). CONCLUSIONS: Brain change with aging is characterized by extensive shrinkage of white matter. Baseline white matter microstructure as indexed by DTI was associated with some of the observed regional volume loss. The findings suggest that both white matter volume loss and microstructural alterations should be considered more prominently in models of aging and neurodegenerative diseases.

The Effect of Mindfulness Meditation on Impulsivity and its Neurobiological Correlates in Healthy Adults.

Interest has grown in using mindfulness meditation to treat conditions featuring excessive impulsivity. However, while prior studies find that mindfulness practice can improve attention, it remains unclear whether it improves other cognitive faculties whose deficiency can contribute to impulsivity. Here, an eight-week mindfulness intervention did not reduce impulsivity on the go/no-go task or Barratt Impulsiveness Scale (BIS-11), nor produce changes in neural correlates of impulsivity (i.e. frontostriatal gray matter, functional connectivity, and dopamine levels) compared to active or wait-list control groups. Separately, long-term meditators (LTMs) did not perform differently than meditation-naïve participants (MNPs) on the go/no-go task. However, LTMs self-reported lower attentional impulsivity, but higher motor and non-planning impulsivity on the BIS-11 than MNPs. LTMs had less striatal gray matter, greater cortico-striatal-thalamic functional connectivity, and lower spontaneous eye-blink rate (a physiological dopamine indicator) than MNPs. LTM total lifetime practice hours (TLPH) did not significantly relate to impulsivity or neurobiological metrics. Findings suggest that neither short- nor long-term mindfulness practice may be effective for redressing impulsive behavior derived from inhibitory motor control or planning capacity deficits in healthy adults. Given the absence of TLPH relationships to impulsivity or neurobiological metrics, differences between LTMs and MNPs may be attributable to pre-existing differences.

An Examination of Brain Abnormalities and Mobility in Individuals with Mild Cognitive Impairment and Alzheimer's Disease.

Background: Mobility changes are concerning for elderly patients with cognitive decline. Given frail older individuals' vulnerability to injury, it is critical to identify contributors to limited mobility. Objective: To examine whether structural brain abnormalities, including reduced gray matter volume and white matter hyperintensities, would be associated with limited mobility among individuals with cognitive impairment, and to determine whether cognitive impairment would mediate this relationship. Methods: Thirty-four elderly individuals with mild cognitive impairment (MCI) and Alzheimer's disease underwent neuropsychological evaluation, mobility assessment, and structural brain neuroimaging. Linear regression was conducted with predictors including gray matter volume in six regions of interest (ROI) and white matter hyperintensity (WMH) burden, with mobility measures as outcomes. Results: Lower gray matter volume in caudate nucleus was associated with slower speed on a functional mobility task. Higher cerebellar volume was also associated with slower functional mobility. White matter hyperintensity burden was not significantly associated with mobility. Conclusion: Our findings provide evidence for associations between subcortical gray matter volume and speed on a functional mobility task among cognitively impaired individuals.

Microstructural white matter alterations in preclinical Alzheimer's disease detected using free water elimination diffusion tensor imaging.

Brain changes associated with Alzheimer's disease (AD) begin decades before disease diagnosis. While ß-amyloid plaques and neurofibrillary tangles are defining features of AD, neuronal loss and synaptic pathology are closely related to the cognitive dysfunction. Brain imaging methods that are tuned to assess degeneration of myelinated nerve fibers in the brain (collectively called white matter) include diffusion tensor imaging (DTI) and related techniques, and are expected to shed light on disease-related loss of structural connectivity. Participants (N = 70, ages 47-76 years) from the Wisconsin Registry for Alzheimer's Prevention study underwent DTI and hybrid diffusion imaging to determine a free-water elimination (FWE-DTI) model. The study assessed the extent to which preclinical AD pathology affects brain white matter. Preclinical AD pathology was determined using cerebrospinal fluid (CSF) biomarkers. The sample was enriched for AD risk (APOE ε4 and parental history of AD). AD pathology assessed by CSF analyses was significantly associated with altered microstructure on both DTI and FWE-DTI. Affected regions included frontal, parietal, and especially temporal white matter. The f-value derived from the FWE-DTI model appeared to be the most sensitive to the relationship between the CSF AD biomarkers and microstructural alterations in white matter. These findings suggest that white matter degeneration is an early pathological feature of AD that may have utility both for early disease detection and as outcome measures for clinical trials. More complex models of microstructural diffusion properties including FWE-DTI may provide increased sensitivity to early brain changes associated with AD over standard DTI.

Cortical thinning in psychopathy.

OBJECTIVE: Psychopathy is a personality disorder associated with severely antisocial behavior and a host of cognitive and affective deficits. The neuropathological basis of the disorder has not been clearly established. Cortical thickness is a sensitive measure of brain structure that has been used to identify neurobiological abnormalities in a number of psychiatric disorders. The authors assessed cortical thickness and corresponding functional connectivity in psychopathic prison inmates. METHOD: Using T1 MRI data, the authors computed cortical thickness maps in a sample of adult male prison inmates selected on the basis of psychopathy diagnosis (21 psychopathic inmates and 31 nonpsychopathic inmates). Using restingstate functional MRI data from a subset of these inmates (20 psychopathic inmates and 20 nonpsychopathic inmates), the authors then computed functional connectivity within networks exhibiting significant thinning among psychopaths. RESULTS: Relative to nonpsychopaths, psychopaths had significantly thinner cortex in a number of regions, including the left insula and dorsal anterior cingulate cortex, the left and right precentral gyri, the left and right anterior temporal cortices, and the right inferior frontal gyrus. These neurostructural differences were not due to differences in age, IQ, or substance use. Psychopaths also exhibited a corresponding reduction in functional connectivity between the left insula and the left dorsal anterior cingulate cortex. CONCLUSIONS: Psychopathy is associated with a distinct pattern of cortical thinning and reduced functional connectivity.

Subjective socioeconomic status predicts human ventral striatal responses to social status information.

The enormous influence of hierarchical rank on social interactions [1] suggests that neural mechanisms exist to process status-related information [2] and ascribe value to it. The ventral striatum is prominently implicated in processing value and salience, independent of hedonic properties [3, 4], and a functional magnetic resonance imaging (fMRI) study of social status perception in humans demonstrated that viewing higher-ranked compared to lower-ranked individuals evokes a ventral striatal response [5], indicative of a greater assignment of value/salience to higher status. Consistent with this interpretation, nonhuman primates value information associated with higher-ranked conspecifics more than lower-ranked, as illustrated using a choice paradigm in which monkeys preferentially take the opportunity to view high-status monkeys [6]. Interestingly, this status-related value assignment in nonhuman primates is influenced by one's own hierarchical rank: high-status monkeys preferentially attend to conspecifics of high status, whereas low-status monkeys will also attend to other low-status monkeys [7]. Complementary to these findings, using fMRI and a social status judgment task in humans, we suggest a neurobiological mechanism by which one's own relative hierarchical rank influences the value attributed to particular social status information by demonstrating that one's subjective socioeconomic status differentially influences ventral striatal activity during processing of status-related information.

Can robotic assisted laparoscopic prostatectomy be recommended to obese patients?

Experienced robotic surgeons report lower estimated blood loss (EBL) and transfusion rates with similar clinical outcomes for robotic assisted laparoscopic radical prostatectomy (RALP) compared to open radical retropubic prostatectomy (RRP). We reviewed our experience with RALP to investigate how to counsel overweight and obese patients being considered for RALP regarding risk of major perioperative complications, oncological outcomes, and short-term recovery. We reviewed the data on 1,513 patients who underwent RALP by one of four experienced robotic surgeons between June 2003 and November 2006. These patients were categorized as normal, overweight, obese, and severely obese based on body mass index (BMI). Of these patients, 361 (23.9%) had a BMI under 25, 794 (52.5%) had a BMI between 25 and 30 (overweight), 290 (19.2%) had a BMI between 30 and 35 (obese), and 68 (4.5%) had a BMI over 35 (severely obese). Records were examined and analyzed with respect to BMI for major intra- and perioperative complications, operative time, margin status, EBL, transfusion rates, and length of hospital stay. Increasing BMI was associated with longer operative time, with mean operative times of 2.7, 2.8, 3.1, and 3.3 h for normal, overweight, obese and severely obese patients, respectively (P < 0.0001). Higher blood loss, though not clinically significant, was also associated with increased BMI, with obese and severely obese patients losing a median of 250 mL of blood compared to 200 mL in overweight and non-overweight patients (P < 0.0001). Transfusion rates, intra- and perioperative complications, margin status, and length of stay were not found to be associated with BMI group. Robotic assisted laparoscopic radical prostatectomy in experienced hands can be safely recommended to eligible patients regardless of BMI status.